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Vaccines, Blood & Biologics

11/1/2007 Fax - Rotarix

Deficiencies that require Additional Information from the Sponsor

  1. In section 2 of Container Closure System you have stated that "Raw materials used in the transfer device are of pharmacopeia quality in compliance with -- pharmacopeia and ISO 10993 guidelines." Certain materials such as ------------- are mentioned in the description of the Transfer Adapter. We believe that generic class alone (e.g. -------------) is not adequate because there are many formulations of material composition. Please provide a complete listing of all device materials (trade name and chemical formula) and manufacturer. Please also provide the list of materials, name of the manufacturer for glass syringes, syringe plunger stoppers, plunger rods for the syringes and the backstops for the syringes. Please also include the exact name, composition, manufacturer of ---------------------- used on the syringe.
  2. The description, tests, specifications you have provided of the Container Closure System do not state that any biocompatibility was performed according to the ISO 10993 or an equivalent standard. Even though the syringe and the adapter may not be touching the patient, they are contacting the vaccine. Hence untested devices and their materials such as the ------------------ may contaminate the vaccine being administered to the patient. Please provide biocompatibility test results obtained by testing representative samples of final finished product (including the syringe and the adapter). Please also identify lot number tested and date of manufacture. Please also provide us with testing protocols with end points: Cytotoxicity, Sensitization, Irritation or Intracutaneous reactivity. The Agency recommends that you conduct biocompatibility testing as described in the guidance, Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part-1: Evaluation and Testing,
  3. In the Container Closure System section you state, "Both tip caps and plunger rubber contains dry natural latex. The transfer adapter is latex-free." A user or a patient can have an allergic reaction to products containing latex. Therefore in order for your device to be latex-free, please certify that your product does not contain latex, is manufactured in a latex free environment, and that the raw materials used to make your product have not been exposed to latex proteins. For devices containing natural latex, please refer to 21 CFR 801.437 User Labeling for devices that contain natural rubber.
  4. In section 2 of the Container Closure System section you have provided tables containing the tests and specifications for glass syringes. FDA recommends conformance to FDA recognized standard(s) to ensure that the device has been tested according to the international consensus tests outlined in the standards. Please confirm if the glass syringe conforms to: ISO 7886-1:1993 Sterile hypodermic syringes for single use -- Part 1: Syringes for manual use, ISO 594-1 Conical fittings with a 6 % (Luer) taper for syringes, needles and certain other medical equipment -- Part 1: General requirements, and / or ISO 594-2 Conical Fittings with a 6% (Luer) Taper for Syringes, Needles, and Certain other Medical Equipment. Please also verify if the Enteral Transfer Adapter conforms to any FDA recognized standards.
  5. In section 1.2 of the Container Closure System, you have stated that the vaccine is filled in a sterile syringe; however the syringe plunger rod is not sterilized. The FDA expects that the syringe, plunger stoppers, plunger rods, backstops, enteral transfer adapter (ETA) will all be sterilized since there is a possibility of contamination of the vaccine if these components are not sterile. Also the sterilization must be performed on final finished products (entire syringe and its components, and ETA). Therefore please provide us with the following:


    1. Sterilization method description (e.g. ---------------------)
    2. ----, for --------- (e.g., -----------)
    3. Sterilant residuals remaining on the device. (For --, the maximum levels of residuals of --------------------------- that remain on the device (note: not to include ------------------------------- residual level because the recognized standard, ---------------------------------------------------------------------- ---------------------------------------------------------------------------------- -------------------------
    4. A description of the Validation Method for the sterilization cycle (not data). For example, --------------cycle method, bioburden method, combination method
    5. Sterility assurance level (SAL). (e.g., 10-6 for all devices.
    6. If you have labeled your devices as "Pyrogen Free". Please provide a description of the method used and bench testing to support your claim.

Luba Vujcic
301 827-3070

Contact FDA

(800) 835-4709
(240) 402-8010
Consumer Affairs Branch (CBER)

Division of Communication and Consumer Affairs

Office of Communication, Outreach and Development

Food and Drug Administration

10903 New Hampshire Avenue

Building 71 Room 3103

Silver Spring, MD 20993-0002

Page Last Updated: 03/15/2010
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